This proposal examines the role of certain infectious, immunologic and genetic determinants in the pathogenesis of inflammatory bowel disease (IBD). It includes cytotoxicity studies utilizing various mononuclear cell populations as effectors and intestinally derived cells grown in tissue culture as targets. Patients with IBD and their families are being HLA phenotyped to search for disease association or HLA segregation. The influence of HLA phenotype on cellular cytotoxicity is being evaluated. The effect of membrane preparations of putative cytopathic agents associated with IBD on the function of cultured lymphocytes is also being assessed.